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2009 Fiscal Year Final Research Report

Innovative strategies in radiation therapy targeting tumor hypoxia by biological and physical approaches.

Research Project

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Project/Area Number 17016036
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

HIRAOKA Mashiro  Kyoto University, 医学研究科, 教授 (70173218)

Co-Investigator(Kenkyū-buntansha) KONDOH Shinae  京都大学, 医学研究科, 教授 (40314182)
MIZOWAKI Takashi  京都大学, 医学研究科, 講師 (90314210)
SHIBUYA Keiko  京都大学, 医学研究科, 助教 (50335262)
ITASAKA Satoshi  京都大学, 医学研究科, 助教 (90378654)
HARADA Hirohsi  京都大学, 医学研究科, 講師 (80362531)
Project Period (FY) 2005 – 2009
Keywords低酸素 / イメージング / 強度変調放射線治療 / 蛋白質製剤 / 同所性移植モデル
Research Abstract

Hypoxic fraction in solid malignant tumor is strongly correlated with poor treatment effects of irradiation and prognosis. In order to develop an innovative radiation therapy strategy to overcome intra-tumor hypoxia, we have accomplished (1)evaluation of the presence and dynamic change of hypoxic region in the lung orthotopic tumor model, (2) development of the hypoxia targeted protein drug and the promotion of translational research, (3)optimization of the combination of the hypoxia targeted protein drug and irradiation, (4)establishment of Intensity Modulated Radiation Therapy(IMRT) method for simultaneous dose escalation in intra-tumor hypoxic region, (5)development of a treatment planning technique which can handle target motion and a moving phantom system for dose verification of moving target.

  • Research Products

    (38 results)

All 2009 2008 2007 2006 2005

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (12 results) Book (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] The HIF-1-active microenvironment: an environmental target for cancer therapy.2009

    • Author(s)
      Kizaka-Kondoh S., Tanaka S., Harada H., Hiraoka M.
    • Journal Title

      Adv Drug Deliv Rev. 61(7-8)

      Pages: 623-632

    • Peer Reviewed
  • [Journal Article] Selective killing of hypoxia-inducible factor-1-active cells improves survival in a mouse model of invasive and metastatic pancreatic cancer.2009

    • Author(s)
      Kizaka-Kondoh S., Itasaka S., Zeng L., Tanaka S., Zhao T., Takahashi Y., Shibuya K., Hirota K., Semenza G.L., Hiraoka M.
    • Journal Title

      Clin Cancer Res. 15(10)

      Pages: 3433-3441

    • Peer Reviewed
  • [Journal Article] Imaging and targeting of HIF-1 active microenvironment.2009

    • Author(s)
      Kizaka-Kondoh S., Tanaka S., Hiraoka M.
    • Journal Title

      Journal of Toxicologic Pathology 22(2)

      Pages: 93-100

    • Peer Reviewed
  • [Journal Article] Imaging probe for tumor malignancy.2009

    • Author(s)
      Tanaka S., Kizaka-Kondoh S., Hiraoka M.
    • Journal Title

      Progress in Biomedical Optics and Imaging 10(30)

      Pages: 719014-1~7

    • Peer Reviewed
  • [Journal Article] Impact of motion velocity on four-dimensional target volumes: a phantom study.2009

    • Author(s)
      Nakamura M., Narita Y., Sawada A., Matsugi K., Nakata M., Matsuo Y., Mizowaki T., Hiraoka M.
    • Journal Title

      Med Phys. 36(5)

      Pages: 1610-1617

    • Peer Reviewed
  • [Journal Article] Initial validations for pursuing irradiation using a gimbals tracking system.2009

    • Author(s)
      Takayama K., Mizowaki T., Kokubo M., Kawada N., Nakayama H., Narita Y., Nagano K., Kamino Y., Hiraoka M.
    • Journal Title

      Radiother Oncol. 93(1)

      Pages: 45-9

    • Peer Reviewed
  • [Journal Article] New algorithm to simulate organ movement and deformation for four-dimensional dose calculation based on a three-dimensional CT and fluoroscopy of the thorax.2009

    • Author(s)
      Miyabe Y., Narita Y., Mizowaki T., Matsuo Y., Takayama K., Takahashi K., Kaneko S., Kawada N., Maruhashi A., Hiraoka M.
    • Journal Title

      Med Phys. 36(10)

      Pages: 4328-4339

    • Peer Reviewed
  • [Journal Article] Comparisons of the impact of systematic uncertainties in patient setup and prostate motion on doses to the target among different plans for definitive external-beam radiotherapy for prostate cancer.2008

    • Author(s)
      Zhu S., Mizowaki T., Norihisa Y., Takayama K., Nagata Y., Hiraoka M.
    • Journal Title

      Int J Clin Oncol. 13(1)

      Pages: 54-61

    • Peer Reviewed
  • [Journal Article] Development of a three-dimensionally movable phantom system for dosimetric verifications.2008

    • Author(s)
      Nakayama H., Mizowaki T., Narita Y., Kawada N., Takahashi K., Mihara K., Hiraoka, M.
    • Journal Title

      Med Phys. 35(5)

      Pages: 643-1650

    • Peer Reviewed
  • [Journal Article] Geometrical differences in target volumes between slow CT and 4D CT imaging in stereotactic body radiotherapy for lung tumors in the upper and middle lobe.2008

    • Author(s)
      Nakamura M., Narita Y., Matsuo Y., Narabayashi M., Nakata M., Yano S., Miyabe Y, Matsugi K., Sawada A., Norihisa Y., Mizowaki T., Nagata Y., Hiraoka M.
    • Journal Title

      Med Phys. 35(9)

      Pages: 4142-4148

    • Peer Reviewed
  • [Journal Article] TS-1 enhances the effect of radiotherapy by suppressing radiation-induced hypoxia-inducible factor-1 activation and inducing endothelial cell apoptosis.2008

    • Author(s)
      Zeng L., Ou G., Itasaka S., Harada H., Xie X., Shibuya K., Kizaka-Kondoh S., Morinibu A., Shinomiya K., Hiraoka M.
    • Journal Title

      Cancer Sci. 99(11)

      Pages: 2327-2335

    • Peer Reviewed
  • [Journal Article] An integrated Monte Carlo dosimetric verification system for radiotherapy treatment planning.2007

    • Author(s)
      Yamamoto T., Mizowaki T., Miyabe Y., Takegawa H., Narita Y., Yano S., Nagata Y., Teshima T., Hiraoka M.
    • Journal Title

      Phys Med Biol 52(7)

      Pages: 1991-2008

    • Peer Reviewed
  • [Journal Article] Hypoxia inducible factor-1 influences sensitivity to paclitaxel of human lung cancer cell lines under normoxic conditions.2007

    • Author(s)
      Zeng L., Kizaka-Kondoh S., Itasaka S., Xie X., Inoue M., Tanimoto K., Shibuya K., Hiraoka M
    • Journal Title

      Cancer Sci. 98(9)

      Pages: 1394-401

    • Peer Reviewed
  • [Journal Article] Adenovirus-mediated hypoxia-targeting cytosine deaminase gene therapy enhances radiotherapy in tumour xenografts.2007

    • Author(s)
      Liu J., Harada H., Ogura M., Shibata T., Hiraoka, M.
    • Journal Title

      Br J Cancer 96(12)

      Pages: 1871-1878

    • Peer Reviewed
  • [Journal Article] Significance of HIF-1-active cells in angiogenesis and radioresistance.2007

    • Author(s)
      Harada, H., Kizaka-Kondoh, S., Li, G., Itasaka, S., Shibuya, K., Inoue, M., Hiraoka, M.
    • Journal Title

      Oncogene 26(54)

      Pages: 7508-7516

    • Peer Reviewed
  • [Journal Article] The combination of hypoxia-response enhancers and an oxygen-dependent proteolytic motif enables real-time imaging of absolute HIF-1 activity in tumor xenografts.2007

    • Author(s)
      Harada H., Kizaka-Kondoh S., Itasaka S., Shibuya K., Morinibu A., Shinomiya K., Hiraoka M.
    • Journal Title

      Biochem Biophys Res Commun 360(4)

      Pages: 791-6

    • Peer Reviewed
  • [Journal Article] Development of a novel fluorescent imaging probe for tumor hypoxia by use of a fusion protein with oxygen-dependent degradation domain of HIF-1α.2007

    • Author(s)
      Tanaka S., Kizaka-Kondoh S., Harada H., Hiraoka M.
    • Journal Title

      Progress in Biomedical Optics and Imaging 8(26)

      Pages: 64490Y1-64490Y8

    • Peer Reviewed
  • [Journal Article] Antitumor protein therapy; application of the protein transduction domain to the development of a protein drug for cancer treatment.2006

    • Author(s)
      Harada H., Kizaka-Kondoh S., Hiraoka M.
    • Journal Title

      Breast Cancer 13(1)

      Pages: 16-26

    • Peer Reviewed
  • [Journal Article] Mechanism of hypoxia-specific cytotoxicity of procaspase-3 fused with a VHL-mediated protein destruction motif of HIF-1alpha containing Pro564.2006

    • Author(s)
      Harada H., Kizaka-Kondoh S., Hiraoka M.
    • Journal Title

      FEBS Lett. 580(24)

      Pages: 5718-22

    • Peer Reviewed
  • [Journal Article] Optical imaging of tumor hypoxia and evaluation of efficacy of a hypoxia-targeting drug in living animals.2005

    • Author(s)
      Harada H., Kizaka-Kondoh S., Hiraoka M.
    • Journal Title

      Mol Imaging 4(3)

      Pages: 182-93

    • Peer Reviewed
  • [Journal Article] A tumor-specific gene therapy strategy targeting dysregulation of the VHL/HIF pathway in renal cell carcinomas.2005

    • Author(s)
      Ogura M., Shibata T., Yi J., Liu J., Qu R., Harada H., Hiraoka M.
    • Journal Title

      Cancer Sci. 96(5)

      Pages: 288-94

    • Peer Reviewed
  • [Presentation] High Dose Local Irradiation to T3-4N0M0 Prostate Cancer with Intensity-modulated Radiotherapy Combined with Neoadjuvant Hormonal Therapy.2009

    • Author(s)
      Takashi Mizowaki
    • Organizer
      51st ASTRO Annual Meeting
    • Place of Presentation
      シカゴ米国
    • Year and Date
      20091101-20091105
  • [Presentation] High dose local irradiation to locally advanced prostate cancer with intensity-modulated radiotherapy combined with neoadjuvant hormonal therapy.2009

    • Author(s)
      Takashi Mizowaki, Osamu Ogawa, Masahiro Hiraoka., (他5名)
    • Organizer
      2009 Genitourinary Cancers Symposium: A Multidisciplinary Approach
    • Place of Presentation
      Orlando, Florida USA
    • Year and Date
      2009-02-26
  • [Presentation] HIF-1活性の可視化による病態イメージング.2009

    • Author(s)
      近藤科江
    • Organizer
      平成20年度5領域合同シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2009-02-02
  • [Presentation] Imaging probe for tumor malignancy.2009

    • Author(s)
      近藤科江
    • Organizer
      SPIE Photonics WEST, BiOS 2009
    • Place of Presentation
      San Jose, CA, USA
    • Year and Date
      2009-01-29
  • [Presentation] HIF-1活性を利用した低酸素領域の生体イメージング.2008

    • Author(s)
      近藤科江
    • Organizer
      第31回分子生物学会年会/第81回日本生化学大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
  • [Presentation] 低酸素誘導転写因子HIF1活性のインビボイメージング.2008

    • Author(s)
      近藤科江
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
  • [Presentation] Imaging and targeting HIF-1-active hypoxic cells.2008

    • Author(s)
      Kizaka-Kondoh S.
    • Organizer
      International Society on Oxygen Transport to Tissue 2008
    • Place of Presentation
      Sapporo, Japan.
    • Year and Date
      2008-08-07
  • [Presentation] 強度変調放射線治療の実施に向けて臨床的視点から見たIMRT治療計画.2008

    • Author(s)
      溝脇尚志
    • Organizer
      第18回高精度外部放射線照射研究会
    • Place of Presentation
      福岡
    • Year and Date
      2008-07-26
  • [Presentation] Intensity-modulated radiotherapy for locally advanced prostate caner.2008

    • Author(s)
      Takashi Mizowaki, Osamu Ogawa, Masahiro Hiraoka., (他5名)
    • Organizer
      14th Workshop of the Japanese-German Radiological Affiliation.
    • Place of Presentation
      Dresden Germany
    • Year and Date
      2008-05-31
  • [Presentation] 前立腺癌(放射線治療)2008

    • Author(s)
      溝脇尚志
    • Organizer
      第67回日本医学放射線学会
    • Place of Presentation
      横浜(教育講演)
    • Year and Date
      2008-04-05
  • [Presentation] Current status of Intensity-modulated radiotherapy (IMRT) for prostate cancer in Japan.2007

    • Author(s)
      Mizowaki T.
    • Organizer
      Tri-lateral symposium on Radiation Oncology.
    • Place of Presentation
      Beijing, China
    • Year and Date
      2007-11-14
  • [Presentation] 泌尿器科腫瘍の先端的治療前立腺癌に対する強度変調放射線治療(IMRT)2007

    • Author(s)
      溝脇尚志、高山賢二、則久佳毅、平岡眞寛、賀本敏行、中村英二郎、小川修
    • Organizer
      第95回日本泌尿器科学会学総会シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2007-04-14
  • [Book] EBM泌尿器疾患の治療2009-2010 後藤百力, 他編集 --Low risk 前立腺癌に対する放射線治療:IMRTとシード治療の優劣は?2009

    • Author(s)
      溝脇尚志
    • Total Pages
      16-21
    • Publisher
      中外医学社
  • [Book] 小動物を用いた光イメージング研究の現状。「ナノメデイシン-ナノテクの医療応用」宇理須恒雄編集2008

    • Author(s)
      近藤科江、平岡眞寛
    • Total Pages
      95-98
    • Publisher
      オーム社
  • [Book] インフォームドコンセントのための図説シリーズ前立腺癌吉田修監修-放射線療法1外照射2008

    • Author(s)
      溝脇尚志、平岡真寛
    • Total Pages
      101-103
    • Publisher
      医薬ジャーナル社
  • [Patent(Industrial Property Rights)] 有酸素条件下の細胞で不安定化するタンパク質をコードするDNA2008

    • Inventor(s)
      平岡真寛・近藤科江・原田浩
    • Industrial Property Rights Holder
      平岡真寛・近藤科江
    • Industrial Property Number
      特許・特許第4130955号
    • Acquisition Date
      2008-06-06
  • [Patent(Industrial Property Rights)] 病態の状態をリアルタイムで観察可能なモデル動物とそれを可能にする遺伝子構築物及びその使用2006

    • Inventor(s)
      近藤科江・原田浩・山田秀一・平岡真寛
    • Industrial Property Rights Holder
      有限会社ナノファクトリー
    • Industrial Property Number
      特許・PCT/JP2006/304701
    • Filing Date
      2006-03-10

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Published: 2011-06-18   Modified: 2016-04-21  

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